In the U.S. alone, cancer affects approximately 11.7 million adults and children, and this year, more than 1.5 million new cases will be diagnosed (American Cancer Society. Cancer Facts & Figures 2011. Atlanta: American Cancer Society; 2011). Over 500,000 Americans are expected to die from cancer in 2011, more than 1,300 people per day.
Currently, cancer therapy involves surgery, chemotherapy and/or radiation treatment or eradicate cancerous cells in a patient (see, for example, Stockdale, 1998, “Principles of Cancer Patient Management”, in Scientific American: Medicine, vol. 3, Rubenstein and Federman, eds., Chapter 12, Section IV). All of these approaches pose significant drawbacks for the patient. Surgery, for example, can be contraindicated due to the health of the patient or can be unacceptable to the patient. Additionally, surgery might not completely remove the neoplastic tissue. Radiation therapy is effective only when the irradiated cancerous tissue exhibits a higher sensitivity to radiation than normal tissue, and radiation therapy can also often elicit serious side effects. (Id.) With respect to chemotherapy, there are a variety of chemotherapeutic agents available for treatment of neoplastic disease. However, despite the availability of a variety of chemotherapeutic agents, chemotherapy has many drawbacks (see, for example, Stockdale, 1998, “Principles Of Cancer Patient Management” in Scientific American Medicine, vol. 3, Rubenstein and Federman, eds., ch. 12, sect. 10). Almost all chemotherapeutic agents are toxic, and chemotherapy can cause significant, and often dangerous, side effects, including severe nausea, bone marrow depression, immunosuppression, etc. Additionally, many tumor cells are resistant or develop resistance to chemotherapeutic agents through multi-drug resistance.
The development of novel or improved therapies focuses on preventing angiogenesis, growth or regrowth and metastasis of tumors as these are key processes that must be halted in order to successfully treat or cure a cancer. These processes can be promoted by bone marrow-derived cells (BMDCs), e.g. myelomonocytes and macrophages which have migrated into the tumor or the surrounding tissue. Recruitment of BMDCs to a tumor can be triggered by certain chemotherapeutics, vascular disruption treatments, or radiation therapy (Shaked Y, Ciarrocchi A, Franco M, et al. Science 2006; 313:1785-7 Shaked Y, Henke E, Roodhart J M, et al, Cancer Cell 2008; 14:263-73). One mechanism believed to drive recruitment of BMDCs to tumors is the CXCR4-CXCL12 signal pathway. CXCR4 is the receptor for CXCL12 and is suspected of controlling cancer cell migration and metastasis as well as BDMC infiltration into tissues14.
An increased understanding of the kinetics and mechanisms of the CXCR4-CXCL12 pathway and its promotion of BMDC infiltration of tumors will enable more effective therapies, improved combination therapy strategies, and allow lower and fewer doses of anti-cancer treatments without compromising efficacy, thereby avoiding the detrimental side effects of chemotherapy and radiation therapy.